Metabolic Syndrome: A Narrative Review from the Oxidative Stress to the Management of Related Diseases

Abstract

Metabolic syndrome (MS) is a growing disorder affecting thousands of people worldwide, especially in industrialised countries, increasing mortality. Oxidative stress, hyperglycaemia, insulin resistance, inflammation, dysbiosis, abdominal obesity, atherogenic dyslipidaemia and hypertension are important factors linked to MS clusters of different pathologies, such as diabesity, cardiovascular diseases and neurological disorders. All biochemical changes observed in MS, such as dysregulation in the glucose and lipid metabolism, immune response, endothelial cell function and intestinal microbiota, promote pathological bridges between metabolic syndrome, diabesity and cardiovascular and neurodegenerative disorders. This review aims to summarise metabolic syndrome's involvement in diabesity and highlight the link between MS and cardiovascular and neurological diseases. A better understanding of MS could promote a novel strategic approach to reduce MS comorbidities.

Keywords: cardiovascular diseases; diabesity; dysbiosis; gut microbiota; metabolic syndrome; neurodegeneration.

Figure 1

Metabolic syndrome (MS) related processes. Under pathophysiological conditions, the imbalance between free radicals/oxidants and antioxidant defences leads to oxidative stress. The resulting oxidative stress causes intracellular damage (DNA, lipids, proteins) and redox alteration, inducing the irreversible accumulation of oxidation products that promote endothelial dysfunction, which leads to insulin resistance, hypertension, dyslipidaemia and, ultimately, MS.

Figure 2

Pathophysiology of diabesity. Genetic and environmental factors (lifestyles) regulate the function of the pancreatic islets and the interaction between diabetes and obesity. Hyperglycaemia, resulting from reduced insulin sensitivity due to the reduction of the functional mass of β-cells, is closely related to obesity, which plays a crucial role in oxidative stress and inflammatory metabolic processes, glucotoxicity and lipotoxicity, and is associated with insulin resistance/deficiency.

Figure 3

Influence of the gut microbiota on diabesity. Under normal conditions (eubiosis), the gut is dominated by non-pathogenic microorganisms that are important for physiological interactions with other systems, such as the brain and organs and tissues involved in metabolism, to prevent and combat the progression of metabolic syndrome. Dysbiosis in the gut microbiota, caused by many factors (antibiotics, diet, lifestyle), is associated with metabolic alterations leading to diabetes and related comorbidities. CVD, cardiovascular disease; IEC, intestinal epithelial cell; LPS, lipopolysaccharide; SCFA, short chain fatty acid; TJ, tight junction; LDL-C, low-density lipoprotein cholesterol.